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RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study
PURPOSE: To investigate the course of inherited retinal degenerations (IRD) due to mutations in the RPE65 gene. METHODS: This longitudinal multicentric retrospective chart-review study was designed to collect best corrected visual acuity (BCVA), Goldman visual field, optical coherence tomography (OC...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822366/ https://www.ncbi.nlm.nih.gov/pubmed/35129589 http://dx.doi.org/10.1167/iovs.63.2.13 |
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author | Testa, Francesco Murro, Vittoria Signorini, Sabrina Colombo, Leonardo Iarossi, Giancarlo Parmeggiani, Francesco Falsini, Benedetto Salvetti, Anna Paola Brunetti-Pierri, Raffaella Aprile, Giorgia Bertone, Chiara Suppiej, Agnese Romano, Francesco Karali, Marianthi Donati, Simone Melillo, Paolo Sodi, Andrea Quaranta, Luciano Rossetti, Luca Buzzonetti, Luca Chizzolini, Marzio Rizzo, Stanislao Staurenghi, Giovanni Banfi, Sandro Azzolini, Claudio Simonelli, Francesca |
author_facet | Testa, Francesco Murro, Vittoria Signorini, Sabrina Colombo, Leonardo Iarossi, Giancarlo Parmeggiani, Francesco Falsini, Benedetto Salvetti, Anna Paola Brunetti-Pierri, Raffaella Aprile, Giorgia Bertone, Chiara Suppiej, Agnese Romano, Francesco Karali, Marianthi Donati, Simone Melillo, Paolo Sodi, Andrea Quaranta, Luciano Rossetti, Luca Buzzonetti, Luca Chizzolini, Marzio Rizzo, Stanislao Staurenghi, Giovanni Banfi, Sandro Azzolini, Claudio Simonelli, Francesca |
author_sort | Testa, Francesco |
collection | PubMed |
description | PURPOSE: To investigate the course of inherited retinal degenerations (IRD) due to mutations in the RPE65 gene. METHODS: This longitudinal multicentric retrospective chart-review study was designed to collect best corrected visual acuity (BCVA), Goldman visual field, optical coherence tomography (OCT), and electroretinography (ERG) measurements. The data, including imaging, were collected using an electronic clinical research form and were reviewed at a single center to improve consistency. RESULTS: From an overall cohort of 60 Italian patients with RPE65-associated IRD, 43 patients (mean age, 27.8 ± 19.7 years) were included and showed a mean BCVA of 2.0 ± 1.0 logMAR. Time-to-event analysis revealed a median age of 33.8 years and 41.4 years to reach low vision and blindness based on BCVA, respectively. ERG (available for 34 patients) showed undetectable responses in most patients (26; 76.5%). OCT (available for 31 patients) revealed epiretinal membranes in five patients (16.1%). Central foveal thickness significantly decreased with age at a mean annual rate of −0.6%/y (P = 0.044). We identified 43 different variants in the RPE65 gene in the entire cohort. Nine variants were novel. Finally, to assess genotype-phenotype correlations, patients were stratified according to the number of RPE65 loss-of-function (LoF) alleles. Patients without LoF variants showed significantly (P < 0.05) better BCVA compared to patients with one or two LoF alleles. CONCLUSIONS: We described the natural course of RPE65-associated IRD in an Italian cohort showing for the first time a specific genotype-phenotype association. Our findings can contribute to a better management of RPE65-associated IRD patients. |
format | Online Article Text |
id | pubmed-8822366 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
spelling | pubmed-88223662022-02-18 RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study Testa, Francesco Murro, Vittoria Signorini, Sabrina Colombo, Leonardo Iarossi, Giancarlo Parmeggiani, Francesco Falsini, Benedetto Salvetti, Anna Paola Brunetti-Pierri, Raffaella Aprile, Giorgia Bertone, Chiara Suppiej, Agnese Romano, Francesco Karali, Marianthi Donati, Simone Melillo, Paolo Sodi, Andrea Quaranta, Luciano Rossetti, Luca Buzzonetti, Luca Chizzolini, Marzio Rizzo, Stanislao Staurenghi, Giovanni Banfi, Sandro Azzolini, Claudio Simonelli, Francesca Invest Ophthalmol Vis Sci Retina PURPOSE: To investigate the course of inherited retinal degenerations (IRD) due to mutations in the RPE65 gene. METHODS: This longitudinal multicentric retrospective chart-review study was designed to collect best corrected visual acuity (BCVA), Goldman visual field, optical coherence tomography (OCT), and electroretinography (ERG) measurements. The data, including imaging, were collected using an electronic clinical research form and were reviewed at a single center to improve consistency. RESULTS: From an overall cohort of 60 Italian patients with RPE65-associated IRD, 43 patients (mean age, 27.8 ± 19.7 years) were included and showed a mean BCVA of 2.0 ± 1.0 logMAR. Time-to-event analysis revealed a median age of 33.8 years and 41.4 years to reach low vision and blindness based on BCVA, respectively. ERG (available for 34 patients) showed undetectable responses in most patients (26; 76.5%). OCT (available for 31 patients) revealed epiretinal membranes in five patients (16.1%). Central foveal thickness significantly decreased with age at a mean annual rate of −0.6%/y (P = 0.044). We identified 43 different variants in the RPE65 gene in the entire cohort. Nine variants were novel. Finally, to assess genotype-phenotype correlations, patients were stratified according to the number of RPE65 loss-of-function (LoF) alleles. Patients without LoF variants showed significantly (P < 0.05) better BCVA compared to patients with one or two LoF alleles. CONCLUSIONS: We described the natural course of RPE65-associated IRD in an Italian cohort showing for the first time a specific genotype-phenotype association. Our findings can contribute to a better management of RPE65-associated IRD patients. The Association for Research in Vision and Ophthalmology 2022-02-07 /pmc/articles/PMC8822366/ /pubmed/35129589 http://dx.doi.org/10.1167/iovs.63.2.13 Text en Copyright 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. |
spellingShingle | Retina Testa, Francesco Murro, Vittoria Signorini, Sabrina Colombo, Leonardo Iarossi, Giancarlo Parmeggiani, Francesco Falsini, Benedetto Salvetti, Anna Paola Brunetti-Pierri, Raffaella Aprile, Giorgia Bertone, Chiara Suppiej, Agnese Romano, Francesco Karali, Marianthi Donati, Simone Melillo, Paolo Sodi, Andrea Quaranta, Luciano Rossetti, Luca Buzzonetti, Luca Chizzolini, Marzio Rizzo, Stanislao Staurenghi, Giovanni Banfi, Sandro Azzolini, Claudio Simonelli, Francesca RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study |
title | RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study |
title_full | RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study |
title_fullStr | RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study |
title_full_unstemmed | RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study |
title_short | RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study |
title_sort | rpe65-associated retinopathies in the italian population: a longitudinal natural history study |
topic | Retina |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822366/ https://www.ncbi.nlm.nih.gov/pubmed/35129589 http://dx.doi.org/10.1167/iovs.63.2.13 |
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